Enantioselective reduction organocatalysis

Subsequent major events, up until the early 1980s, have been reviewed [2], with one of the major reactions involved being that of asymmetric hydrogenation, which is especially useful and efficient. This was first developed using rhodium complexes equipped with chiral mono- or diphosphines [3-6], though many other types of reaction (e.g., hydroformylation, Diels-Alder reaction) are now well controlled in the presence of chiral organometallic catalysts. Over the past few years there has been a clear renewal of interest for organocatalysis [7], and consequently this chapter will review the specific and unusual case of the catalytic enantioselective reduction of C=C, C=0, and C=N double bonds. 

Asymmetric organocatalysis deals with the realization of enantioselective transformations by means of small chiral organic molecules [14]. In this realm, chiral acid catalysis and chiral amino-catalysis represent two well-established research fields featuring a rich portfolio of applications in asymmetric C—C and C—X bond-forming processes and reductions. 

Chiral oxazaborolidine catalysts were applied in various enantioselective transformations including reduction of highly functionalized ketones/ oximes or imines/ Diels-Alder reactions/ cycloadditions/ Michael additions, and other reactions. These catalysts are surprisingly small molecules compared to the practically efficient chiral phosphoric acids, cinchona alkaloids, or (thio)ureas hence, their effectiveness in asymmetric catalysis demonstrates that huge substituents or extensive hydrogen bond networks are not absolutely essential for successful as5unmetric organocatalysis. 

In recent years, several groups have developed enantioselective tandem reactions based on the combination of gold catalysis and organocatalysis. Among them, Gong et al. reported that an achiral gold complex compatibly worked with a chiral phosphoric acid to promote a domino intramolecular hydroamination-reduction reaction, readily transforming... 

The first case in which organocatalysis by halogen bonding was postulated, a report by Bolm et al. in 2008 [124], in fact involves C-X-based halogen-bond donors. As a test reaction, the reduction of quinoline derivatives by a Hantzsch Ester was chosen. Previously, this type of reaction had been reported to proceed enantioselectively with Ir[COD]Cl2/(5)-SegPhos or chiral Brpnsted acids (Scheme 13) [125]. 

As illustrated by the conversion of 8 to 13, organocatalysis can be used to effect the enantioselective construction of polycarbocyclic products. The initial ring prepared in enantiomerically-pure form by organocatalysis can also set the chirality of a polycyclic system. Professor Corey has reported (/. Am. Chem. Soc. 2007, 129, 10346) that Itsimo-Corey reduction of the prochiral diketone 25 led to the ketone 27. Cyclization followed by oxidation and reduction then delivered estrone methyl ether 28. 

Scheme 15.43 Enantioselective fluorination of enamines via organocatalysis coupled with reductive amination.

Asymmetric hydride reduction using Hantzsch ester has recently been extensively explored in organocatalysis using iminium-based catalysts or Brpnsted acid catalysts [72a-c], As an advance to their asymmetric conterion-directed catalysis (ACDC), List and coworkers found that the combination of simple primary amino acids such as L-valine with a chiral phosphoric acid led to an effective primary aminocatalyst for asymmetric transfer hydrogenation of a,P-unsaturated ketones (Scheme 5.43) [72d]. The catalysis could be applied to a range of substrates with good yields and excellent enantioselectivity. 

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